Chuwei Li, Zhang Qian, Hong Zhang, Xie Ge, Li Chen, Mengqi Xue, Ting Tang, Zhaowanyue He, Lu Zheng, Chun Cao, Kemei Zhang, Rujun Ma, Bing Yao
{"title":"O-GlcNAc 通过介导线粒体功能参与衰老卵母细胞的减数分裂。","authors":"Chuwei Li, Zhang Qian, Hong Zhang, Xie Ge, Li Chen, Mengqi Xue, Ting Tang, Zhaowanyue He, Lu Zheng, Chun Cao, Kemei Zhang, Rujun Ma, Bing Yao","doi":"10.1530/REP-24-0138","DOIUrl":null,"url":null,"abstract":"<p><strong>In brief: </strong>O-GlcNAc plays an important role in many age-related diseases. This study shows that O-GlcNAc participates in oocyte aging and that reducing O-GlcNAc levels in aging oocytes improves oocyte quality.</p><p><strong>Abstract: </strong>With an increase in the mean age at parturition worldwide, female reproductive aging has become a key health problem. Advanced maternal age is reflected by decreased oocyte quality; however, the molecular mechanisms of oocyte aging are uncharacterized. O-linked N-acetylglucosamine (O-GlcNAc), a dynamic posttranslational modification, plays a critical role in the development of many age-related diseases; yet, it remains unclear whether and how O-GlcNAc participates in oocyte aging. Here, we found that global O-GlcNAc was elevated in normal biological aging mice oocytes (9 months), which were characterized by meiotic maturation failure and impaired mitochondrial function. Specifically, O-GlcNAc targeted the mitochondrial fission protein dynamic-related protein 1 to mediate mitochondrial distribution in the process of aging. Using the O-GlcNAcase (OGA) pharmacological inhibitor Thiamet-G and Oga knockdown (Oga-KD) to mimic the age-related high O-GlcNAc in young oocytes from 6-8 week-old mice mimicked the phenotype of oocyte aging. Moreover, reducing O-GlcNAc levels in aging oocytes restored spindle organization to improve oocyte quality. Our results demonstrate that O-GlcNAc is a key regulator of meiotic maturation that participates in the progression of oocyte aging.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"O-GlcNAc participates in the meiosis of aging oocytes by mediating mitochondrial function.\",\"authors\":\"Chuwei Li, Zhang Qian, Hong Zhang, Xie Ge, Li Chen, Mengqi Xue, Ting Tang, Zhaowanyue He, Lu Zheng, Chun Cao, Kemei Zhang, Rujun Ma, Bing Yao\",\"doi\":\"10.1530/REP-24-0138\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>In brief: </strong>O-GlcNAc plays an important role in many age-related diseases. This study shows that O-GlcNAc participates in oocyte aging and that reducing O-GlcNAc levels in aging oocytes improves oocyte quality.</p><p><strong>Abstract: </strong>With an increase in the mean age at parturition worldwide, female reproductive aging has become a key health problem. Advanced maternal age is reflected by decreased oocyte quality; however, the molecular mechanisms of oocyte aging are uncharacterized. O-linked N-acetylglucosamine (O-GlcNAc), a dynamic posttranslational modification, plays a critical role in the development of many age-related diseases; yet, it remains unclear whether and how O-GlcNAc participates in oocyte aging. Here, we found that global O-GlcNAc was elevated in normal biological aging mice oocytes (9 months), which were characterized by meiotic maturation failure and impaired mitochondrial function. Specifically, O-GlcNAc targeted the mitochondrial fission protein dynamic-related protein 1 to mediate mitochondrial distribution in the process of aging. Using the O-GlcNAcase (OGA) pharmacological inhibitor Thiamet-G and Oga knockdown (Oga-KD) to mimic the age-related high O-GlcNAc in young oocytes from 6-8 week-old mice mimicked the phenotype of oocyte aging. Moreover, reducing O-GlcNAc levels in aging oocytes restored spindle organization to improve oocyte quality. Our results demonstrate that O-GlcNAc is a key regulator of meiotic maturation that participates in the progression of oocyte aging.</p>\",\"PeriodicalId\":21127,\"journal\":{\"name\":\"Reproduction\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-11-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproduction\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1530/REP-24-0138\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q1\",\"JCRName\":\"DEVELOPMENTAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproduction","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1530/REP-24-0138","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/1 0:00:00","PubModel":"Print","JCR":"Q1","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
O-GlcNAc participates in the meiosis of aging oocytes by mediating mitochondrial function.
In brief: O-GlcNAc plays an important role in many age-related diseases. This study shows that O-GlcNAc participates in oocyte aging and that reducing O-GlcNAc levels in aging oocytes improves oocyte quality.
Abstract: With an increase in the mean age at parturition worldwide, female reproductive aging has become a key health problem. Advanced maternal age is reflected by decreased oocyte quality; however, the molecular mechanisms of oocyte aging are uncharacterized. O-linked N-acetylglucosamine (O-GlcNAc), a dynamic posttranslational modification, plays a critical role in the development of many age-related diseases; yet, it remains unclear whether and how O-GlcNAc participates in oocyte aging. Here, we found that global O-GlcNAc was elevated in normal biological aging mice oocytes (9 months), which were characterized by meiotic maturation failure and impaired mitochondrial function. Specifically, O-GlcNAc targeted the mitochondrial fission protein dynamic-related protein 1 to mediate mitochondrial distribution in the process of aging. Using the O-GlcNAcase (OGA) pharmacological inhibitor Thiamet-G and Oga knockdown (Oga-KD) to mimic the age-related high O-GlcNAc in young oocytes from 6-8 week-old mice mimicked the phenotype of oocyte aging. Moreover, reducing O-GlcNAc levels in aging oocytes restored spindle organization to improve oocyte quality. Our results demonstrate that O-GlcNAc is a key regulator of meiotic maturation that participates in the progression of oocyte aging.
期刊介绍:
Reproduction is the official journal of the Society of Reproduction and Fertility (SRF). It was formed in 2001 when the Society merged its two journals, the Journal of Reproduction and Fertility and Reviews of Reproduction.
Reproduction publishes original research articles and topical reviews on the subject of reproductive and developmental biology, and reproductive medicine. The journal will consider publication of high-quality meta-analyses; these should be submitted to the research papers category. The journal considers studies in humans and all animal species, and will publish clinical studies if they advance our understanding of the underlying causes and/or mechanisms of disease.
Scientific excellence and broad interest to our readership are the most important criteria during the peer review process. The journal publishes articles that make a clear advance in the field, whether of mechanistic, descriptive or technical focus. Articles that substantiate new or controversial reports are welcomed if they are noteworthy and advance the field. Topics include, but are not limited to, reproductive immunology, reproductive toxicology, stem cells, environmental effects on reproductive potential and health (eg obesity), extracellular vesicles, fertility preservation and epigenetic effects on reproductive and developmental processes.